Alessandro Serino

Infertility as a proxy of general male health: results of a cross-sectional survey

OBJECTIVE To evaluate the prevalence, and clinical and seminal impact of comorbidities in white European men presenting for couple infertility. DESIGN Cross-sectional study. SETTING Academic reproductive medicine outpatient clinic. PATIENT(S) Cohort of 2,100 consecutive infertile men (noninterracial infertile couples). INTERVENTION(S) Obtaining complete demographic, clinical, and laboratory data from 2,100 consecutive infertile men with health-significant comorbidities scored via the Charlson comorbidity index (CCI; categorized 0 vs. 1 vs. ≥2) and semen analysis values assessed based on 2010 World Health Organization reference criteria. MAIN OUTCOME MEASURE(S) Assessment of the rate of comorbidities by means of CCI scores and possible associations between CCI, semen and hormonal parameters. RESULT(S) Descriptive statistics and regression models tested the associations among semen parameters, clinical characteristics, and CCI. When assessing general comorbidity prevalence, CCI 0, CCI 1, and CCI ≥2 was found in 1,921 (91.5%), 102 (4.9%), and 77 (3.6%) patients, respectively. Patient age and follicle-stimulating hormone levels increased as the general health status decreased. Conversely, the total testosterone levels and sperm concentration decreased as CCI scores increased. A higher rate of oligozoospermia and nonobstructive azoospermia was observed in patients with CCI ≥1. No differences were observed among the considered comorbidity groups in terms of testicular volume or further hormonal or seminal parameters. Both continuously coded and categorized sperm concentrations were independent predictors of CCI ≥1. Patients with sperm concentration <45.6 million/mL (most informative cutoff value) had a 2.74-fold increased risk of having a CCI ≥1. CONCLUSION(S) Decreased general health status appears to be associated with impaired male reproductive health, including lower sperm concentration, lower total testosterone levels, and higher follicle-stimulating hormone values.

Orgasmic Dysfunction After Robot-assisted Versus Open Radical Prostatectomy.

UNLABELLED Several alterations of orgasmic function that occur after radical prostatectomy (RP) have never been assessed in robot-assisted RP (RARP) series. We sought to assess the prevalence and predictors of recovery from orgasm-associated incontinence (climacturia) and painful orgasm (PO) after RARP and open RP (ORP). Following surgery, sexually active patients who had undergone either RARP or ORP prospectively completed a 28-item questionnaire including sensitive issues regarding sexual function (eg, climacturia and PO). Rates of postoperative climacturia and PO were compared for RARP and ORP patients. Kaplan-Meier analysis was applied to assess estimated rates of recovery from either climacturia or PO after both procedures. Cox regression models tested predictors of recovery from those conditions. Overall, 221 (29.5%) of 749 patients reported climacturia, without differences between RARP and ORP. Conversely, PO was significantly more frequently reported after ORP than after RARP (46 [11.6%] vs 25 [7.1%] patients, respectively; p=0.04). At Kaplan-Meier analysis, recovery from climacturia over time was faster and greater after RARP than after ORP (8.5% vs 5%, respectively, at 24-mo assessment and 48% vs 15%, respectively, at 84-mo assessment; p<0.01). Conversely, no differences were found between groups in terms of postoperative recovery from PO. At multivariable analysis, only RARP achieved independent predictor status for recovery from climacturia after adjusting for other functional outcomes. Conversely, no variables were significantly associated with recovery from postoperative PO. PATIENT SUMMARY Orgasmic modifications such as climacturia and painful orgasm (PO) are frequently reported after radical prostatectomy. Robotic surgery was associated with a lower rate of postoperative PO and with greater and faster recovery from climacturia.

Latest pharmacotherapy options for benign prostatic hyperplasia

Introduction: Benign prostatic hyperplasia (BPH) is a very common condition in men over 50 years, often resulting in lower urinary tract symptoms (LUTS). Medical therapy aims at improving quality of life and preventing complications. The range of drugs available to treat LUTS is rapidly expanding. Areas covered: Silodosin is a relatively new α1-adrenoreceptor antagonist that is selective for α1A-adrenergic receptor. While causing smooth muscle relaxation in the lower urinary tract, it minimizes blood pressure-related adverse effects. Tadalafil, a PDEs type 5 inhibitor, is a drug recently approved for the treatment of BPH/LUTS that challenges the standard therapy with α1-blockers, especially in men with concomitant erectile dysfunction (ED). Mirabegron is the first β3-adrenoceptor agonist approved for the treatment of symptoms of overactive bladder. BPH-related detrusor overactivity (DO) may be successfully targeted by mirabegron. Gonadotropin-releasing hormone antagonists, intraprostatic injections with NX-1207 and vitamin D3 receptor analogues exerted beneficial effects on LUTS but need further evaluation in clinical studies. Expert opinion: Choosing the right treatment should be guided by patients’ symptoms, comorbidities and potential side effects of available drugs. Silodosin is a valid option for elderly and for people taking antihypertensive drugs. BPH patients affected by ED can target both conditions with continuous tadalafil therapy. The encouraging data on mirabegron use in BPH-DO have to be further assessed in larger prospective randomized clinical trials.

Peyronie's Disease and Autoimmunity—A Real-Life Clinical Study and Comprehensive Review

INTRODUCTION Although heavily investigated over the last decades, Peyronies disease (PD) pathogenesis remains unclear. AIM We sought to investigate the association between PD and autoimmune diseases (ADs) in men seeking medical help for sexual dysfunction in the real-life setting. METHODS Complete sociodemographic and clinical data from a homogenous cohort of 1,140 consecutive Caucasian-European men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index and ADs were stratified according to International Classification of Diseases, Ninth Revision classification. MAIN OUTCOME MEASURES Descriptive statistics and multivariate logistic regression models tested the association between ADs and PD. RESULTS PD was diagnosed in 148 (13%) of the 1,140 men; of PD patients, 14 (9.5%) had a comorbid AD; conversely, the rate of ADs in non-PD patients was significantly lower (χ(2) = 24.7; P < 0.01). Both patient age and AD comorbidity achieved multivariable independent predictor status for PD (odds ratio [OR]: 1.05; P < 0.01 and OR: 4.90; P < 0.01, respectively). CONCLUSIONS Our observational findings showed that ADs are highly comorbid with PD in a large cohort of same-race individuals seeking medical help for sexual dysfunction in the real-life setting.

Metabolic syndrome in white European men presenting for primary couple's infertility: investigation of the clinical and reproductive burden.

Despite complex interactions between obesity, dyslipidemia, hyperinsulinaemia, and the reproductive axis, the impact of metabolic syndrome on human male reproductive function has not been analysed comprehensively. Complete demographic, clinical, and laboratory data from 1337 consecutive primary infertile men were analysed. Health‐significant comorbidities were scored with the Charlson Comorbidity Index (categorised 0 vs. 1 vs. 2 or higher). NCEP‐ATPIII criteria were used to define metabolic syndrome. Semen analysis values were assessed based on the 2010 World Health Organisation (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and metabolic syndrome. Metabolic syndrome was found in 128 (9.6%) of 1337 men. Patients with metabolic syndrome were older (p < 0.001) and had a greater Charlson Comorbidity Index of 1 or higher (chi‐square: 15.6; p < 0.001) compared with those without metabolic syndrome. Metabolic syndrome patients had lower levels of total testosterone (p < 0.001), sex hormone‐binding globulin (p = 0.004), inhibin B (p = 0.03), and anti‐Müllerian hormone (p = 0.009), and they were hypogonadal at a higher rate (chi‐square: 32.0; p < 0.001) than patients without metabolic syndrome. Conversely, the two groups did not differ significantly in further hormonal levels, semen parameters, and rate of either obstructive or non‐obstructive azoospermia. At multivariate logistic regression analysis, testicular volume (OR: 0.90; p = 0.002) achieved independent predictor status for WHO pathological semen concentration; conversely, age, Charlson Comorbidity Index scores, metabolic syndrome, and inhibin B values did not. No parameters predicted normal sperm morphology and total progressive motility. Metabolic syndrome accounts for roughly 9% of men presenting for primary couples infertility. Although metabolic syndrome patients have a lower general male health status, semen analysis values seem independent of the presence of metabolic syndrome.

Metabolic syndrome in White-European men presenting for secondary couple's infertility: An investigation of the clinical and reproductive burden

We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Mόllerian hormone (all P ≤ 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P ≤ 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple′s infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

Long-term sexual outcomes after holmium laser enucleation of the prostate: which patients could benefit the most?

Assess rate and predictors of erectile function (EF) outcomes at long-term follow-up (FU) after holmium laser enucleation of the prostate (HoLEP). Cross-sectional analyses were performed on 135 patients with a mean FU of 12 years post HoLEP. Patients completed both a baseline and a FU International Index of Erectile Function (IIEF)-EF domain and the International Prostatic Symptoms Score (IPSS). Postoperative EF outcomes, including rate and predictors of EF improvement considering minimal clinically important differences (MCIDs) criteria, were assessed. Logistic regression models tested the association between predictors and EF. At a mean (median) FU of 152.1 (163) months, patients showed a significant decrease in the IIEF-EF score P<0.01) and significant IPSS improvement (P<0.01). Overall, 50 (37%) patients worsened by at least one IIEF-EF category. Conversel, 23 (17%) patients reported an improvement in postoperative IIEF-EF score; 75 (55.6%) and 10 (7.4%) patients maintained and eventually improved their IIEF-EF category, respectively. Patients reporting a decrease in the postoperative IIEF-EF score were significantly older (P=0.03) and showed a significantly longer mean FU (P<0.01) than those reporting postoperative improvements of IIEF-EF. Nine (6.7%) patients showed significant EF improvement according to MCIDs criteria. Both higher IPSS scores (odds ratio (OR): 1.12; P=0.02) and lower IIEF-EF (OR: 0.88; P<0.01) at baseline, emerged as independent predictors of postoperative EF improvement. HoLEP was associated with a decrease in EF and a persistent amelioration of BPH-related urinary symptoms at long-term FU. Almost one third of patients worsened by at least one IIEF-EF category. However, a clinically meaningful EF improvement was observed in roughly 7% of the individuals. Patients with more severe preoperative urinary symptoms and ED benefited more from HoLEP in terms of EF.

Effects of silodosin on sexual function – realistic picture from the everyday clinical practice

The treatment with α1‐blockers in patients complaining of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is associated with potential adverse events (AEs), thus including ejaculatory dysfunction (EjD). We sought to assess the effects of a 3‐month course of silodosin 8 mg daily dosing on sexual functioning, mainly including ejaculation and orgasm, in a cohort of 100 consecutive sexually active men in the real‐life setting. Patients completed the International Index of Erectile Function‐Orgasmic Function (IIEF‐OF) domain and the International Prostate Symptom Score (IPSS) both at baseline and at survey. Likewise, patients completed a 16‐item self‐administered questionnaire with closed questions also including specific questions regarding treatment‐related adverse events on sexual functioning. Rates and predictors of OF impairment and drug discontinuation were investigated. At survey, silodosin resulted highly effective in improving IPSS‐total and subscales (all p < 0.01). Anejaculation, hypospermia, reduced or absent orgasmic feeling, low sexual desire and erectile dysfunction were subjectively reported by 48 (48%), 23 (23%), 11 (11%), 6 (6%), 7 (7%) and 11 (11%) patients respectively. Overall, a reduction in IIEF‐OF domain score was observed in 64 (64%) patients. Patients with decreased IIEF‐Q9 and/or IIEF‐Q10 scores were significantly younger than those without any decrease (p = 0.02). Of all, only 7% of the patients discontinued silodosin because of anejaculation. Silodosin confirms to be highly effective in patients with LUTS/BPH; of them, almost 70% report either anejaculation or hypospermia, with a concomitant OF impairment in 17% of the patients. Younger patients showed higher rates of a concomitant impairment of ejaculation and OF. Overall, anejaculation caused drug discontinuation in 7% of the patients.

Avanafil - a further step to tailoring patient needs and expectations

ABSTRACT Introduction: Phosphodiesterase type 5 inhibitors (PDE5Is) represent the first-line treatment for erectile dysfunction (ED). Almost one in two patients, however, show some level of treatment dissatisfaction and up to 30% fail to respond to any of the currently available PDE5Is. Recently, the second-generation PDE5I avanafil was launched for the treatment of ED. Areas covered: Pivotal studies of clinical development along with placebo-controlled randomized clinical trials (RCTs) of avanafil in patients with ED were reviewed. Studies concerning the pharmacokinetics and pharmacodynamic of the drug were also analysed. A systematic literature search for English-language studies published up to May 2016 using the Medline database was performed. The search included the terms avanafil and ED. Expert commentary: Avanafil is a potent, highly selective PDE5I whose efficacy is comparable to that of currently available PDE5Is in both naïve and previous PDE5I users. Avanafil is effective within approximately 15 minutes of dosing, thus representing the only PDE5I approved for as-needed use, 15 to 30 minutes before sexual activity. Avanafil has high selectivity for the PDE5 isoenzyme, thus resulting in a lower incidence of drug-related side effects compared to other PDE5Is.

Multiparametric-magnetic resonance imaging second opinion may reduce the number of unnecessary prostate biopsies. Time to improve radiologists’ training programme?

Purpose: To understand the multiparametric magnetic resonance imaging (mpMRI) interreader agreement between radiologists of peripheral and academic centers and the possibility to avoid prostate biopsies according to magnetic resonance imaging second opinion. Patients and Methods: This prospective observational study enrolled 266 patients submitted to mpMRI at nonacademic centers for cancer detection or at active surveillance begin. Images obtained were reviewed by 2 unblinded radiologists with 8 and 5 years’ experience on mpMRI, respectively. We recorded Prostate Imaging Reporting and Data System (PI‐RADS) v2 categories and management strategy changes after mpMRI rereadings. Interreader agreement was assessed by the Cohen kappa. For mpMRI second opinion, positive predictive value and negative predictive value were calculated. Results: In the original readings, no lesions (ie, PI‐RADS < 2) were observed in 17 cases (6.5%). Reported index lesion (IL) PI‐RADS category was 2 in 23 (8.5%), 3 in 85 (32%), 4 in 98 (37%), and 5 in 13 (5%) men, respectively. It is noteworthy that in 30 examinations (11%), an IL was recognized by radiologists, but a suspicious score was not assigned. According to first reading of mpMRI, initial clinical strategy included performing a targeted (226; 85%) or a systematic biopsy (8; 3%), scheduling the patient to an active surveillance program without repeat biopsy (10; 4%), or monitoring prostate‐specific antigen without prostate sampling (22; 8%). The mpMRI rereads did not change IL PI‐RADS category in 91 cases (38.5%), although in 20 (8.5%) and 125 (53%) IL PI‐RADS was upgraded or downgraded, respectively (&kgr; = 0.23). The clinical management changed in 113 patients (48%) (&kgr; = 0.2). Overall, 102 targeted biopsies (51%) were avoided and 72 men (34.5%) were not submitted to biopsy after mpMRI second opinion. Positive predictive value and negative predictive value of the mpMRI rereading were 58% and 91%, respectively. Major limitations of the study are limited‐time follow‐up and the lack of a standard of reference for some men, who were not submitted to biopsy according to mpMRI second opinion. Conclusion: There is an important level of discordance between mpMRI reports. According to imaging second opinion, roughly half of targeted biopsies could be avoidable and 34.5% of men could skipped prostate sampling. Prospective randomized trials are needed to confirm our findings. MICRO‐ABSTRACT In this prospective observational study, we observed a significant level of discordance between multiparametric magnetic resonance imaging of the prostate reports in peripheral and subspecialized centers. If confirmed by further prospective randomized trials, multiparametric magnetic resonance imaging second opinion by expert radiologists could become a useful tool to deliver the best management for patients, avoiding 52% of targeted and 33.5% of total biopsies.